TY - JOUR
T1 - Viral infection prevents diabetes by inducing regulatory T cells through NKT cell-plasmacytoid dendritic cell interplay
AU - Diana, Julien
AU - Brezar, Vedran
AU - Beaudoin, Lucie
AU - Dalod, Marc
AU - Mellor, Andrew
AU - Tafuri, Anna
AU - von Herrath, Matthias
AU - Boitard, Christian
AU - Mallone, Roberto
AU - Lehuen, Agnès
PY - 2011/4/11
Y1 - 2011/4/11
N2 - Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cell-plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-β-producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.
AB - Type 1 diabetes (T1D) is an autoimmune disease resulting from T cell-mediated destruction of insulin-producing β cells, and viral infections can prevent the onset of disease. Invariant natural killer T cells (iNKT cells) exert a regulatory role in T1D by inhibiting autoimmune T cell responses. As iNKT cell-plasmacytoid dendritic cell (pDC) cooperation controls viral replication in the pancreatic islets, we investigated whether this cellular cross talk could interfere with T1D development during viral infection. Using both virus-induced and spontaneous mouse models of T1D, we show that upon viral infection, iNKT cells induce TGF-β-producing pDCs in the pancreatic lymph nodes (LNs). These tolerogenic pDCs convert naive anti-islet T cells into Foxp3+ CD4+ regulatory T cells (T reg cells) in pancreatic LNs. T reg cells are then recruited into the pancreatic islets where they produce TGF-β, which dampens the activity of viral- and islet-specific CD8+ T cells, thereby preventing T1D development in both T1D models. These findings reveal a crucial cooperation between iNKT cells, pDCs, and T reg cells for prevention of T1D by viral infection.
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U2 - 10.1084/jem.20101692
DO - 10.1084/jem.20101692
M3 - Article
C2 - 21444661
AN - SCOPUS:79955738789
SN - 0022-1007
VL - 208
SP - 729
EP - 745
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 4
ER -